Dehydrozingerone protects temozolomide-induced cognitive impairment in normal and C6 glioma rats besides enhancing its anticancer potential

Pathak, Nandini; Cheruku, Sri Pragnya; Rao, Vanishree; Vibhavari, R J A; Sumalatha, Suhani; Gourishetti, Karthik; Rao, C. Mallikarjuna; Kumar, Nitesh

doi:10.1007/s13205-020-02427-7

Cited by 19 publications

(9 citation statements)

References 32 publications

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“…In general, some architectural disturbances and insulted neurons were seen in the hematoxylin and eosin slides of the hippocampus of temozolomide and temozolomide + l -Dopa 25 mg/kg groups. Although this finding is in accordance with the results of our behavioral and molecular tests, histologically, as Pathak et al . (2020) showed, the differences between temozolomide and other groups appear to be negligible.…”

Section: Discussionsupporting

confidence: 94%

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Effect of l-Dopa in acute temozolomide-induced cognitive impairment in male mice: a possible antineuroinflammatory role

Salarinejad¹,

Esmaeilpour²,

Shabani³

et al. 2023

Behavioural Pharmacology

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Temozolomide is used commonly in the treatment of some types of cancers, but it may also result in cognitive impairments such as memory deficits. l-Dopa, a well known medicine for the central nervous system, has been shown to have positive effects on some cognitive disorders. Here we sought to investigate the effect of l-Dopa on temozolomide-induced cognitive impairments. BALB/c mice were subjected to 3-days temozolomide and 6-days concomitant l-Dopa/benserazide administration in six groups (control, l-Dopa 25 mg/kg, l-Dopa 75 mg/kg, temozolomide, temozolomide + l-Dopa 25 mg/kg, and temozolomide + l-Dopa 75 mg/kg). Open field test, object location recognition, novel object recognition test, and shuttle-box test were carried out to determine the locomotor, anxiety-like behavior, and memory function of subjects. TNF-α and brain-derived neurotrophic factor (BDNF) gene expression in the hippocampus was measured by real-time PCR. Mice treated with temozolomide showed recognition memory impairment, along with hippocampal TNF-α and BDNF mRNA expression level raise, and detection of histological insults in hematoxylin and eosin hippocampal slides. Mice that received temozolomide + l-Dopa showed normal behavioral function and lower TNF-α and BDNF hippocampal mRNA expression levels, and histologically normal hippocampal CA1 region in comparison with mice in the temozolomide group. Our results provide evidence that l-Dopa prevents temozolomide-induced recognition memory deficit in mice at the acute phase probably via l-Dopa antineuroinflammatory effects.

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Section: Discussionsupporting

confidence: 94%

“…Temozolomide by different protocols, mediates learning and memory impairments. Pathak et al . (2020), in one of these studies, showed temozolomide-treated rats explore novel objects less than familiar ones.…”

Section: Discussionmentioning

confidence: 99%

Effect of l-Dopa in acute temozolomide-induced cognitive impairment in male mice: a possible antineuroinflammatory role

Salarinejad¹,

Esmaeilpour²,

Shabani³

et al. 2023

Behavioural Pharmacology

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“…Male Wistar rats treated with TMZ (18 mg/kg, i.v) once in 5 days over 32 days showed no preference to the novel object in NORT. The antioxidant analysis showed that TMZ increased MDA and reduced SOD and catalase levels compared with the control group animals (Pathak et al 2020).…”

Section: Temozolomidementioning

confidence: 84%

Animal models of chemotherapy-induced cognitive decline in preclinical drug development

et al. 2021

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Rationale Chemotherapy-induced cognitive impairment (CICI), chemobrain, and chemofog are the common terms for mental dysfunction in a cancer patient/survivor under the influence of chemotherapeutics. CICI is manifested as short/long term memory problems and delayed mental processing, which interferes with a person’s day-to-day activities. Understanding CICI mechanisms help in developing therapeutic interventions that may alleviate the disease condition. Animal models facilitate critical evaluation to elucidate the underlying mechanisms and form an integral part of verifying different treatment hypotheses and strategies. Objectives A methodical evaluation of scientific literature is required to understand cognitive changes associated with the use of chemotherapeutic agents in different preclinical studies. This review mainly emphasizes animal models developed with various chemotherapeutic agents individually and in combination, with their proposed mechanisms contributing to the cognitive dysfunction. This review also points toward the analysis of chemobrain in healthy animals to understand the mechanism of interventions in absence of tumor and in tumor-bearing animals to mimic human cancer conditions to screen potential drug candidates against chemobrain. Results Substantial memory deficit as a result of commonly used chemotherapeutic agents was evidenced in healthy and tumor-bearing animals. Spatial and episodic cognitive impairments, alterations in neurotrophins, oxidative and inflammatory markers, and changes in long-term potentiation were commonly observed changes in different animal models irrespective of the chemotherapeutic agent. Conclusion Dyscognition exists as one of the serious side effects of cancer chemotherapy. Due to differing mechanisms of chemotherapeutic agents with differing tendencies to alter behavioral and biochemical parameters, chemotherapy may present a significant risk in resulting memory impairments in healthy as well as tumor-bearing animals.

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“…Anti-oxidant parameters like catalase, superoxide dismutase (SOD), GSH lipid peroxidation, and total protein were estimated in the liver tissue (Pathak et al 2020 ), using routine laboratory UV spectroscopic and calorimetric methods.…”

Section: Methodsmentioning

confidence: 99%

Amelioration of high-fat diet (HFD) + CCl4 induced NASH/NAFLD in CF-1 mice by activation of SIRT-1 using cinnamoyl sulfonamide hydroxamate derivatives: in-silico molecular modelling and in-vivo prediction

et al. 2022

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Non-alcoholic fatty liver disease (NAFLD) is one of the major hepatic metabolic disorders that occurs because of the accumulation of lipids in hepatocytes in the form of free fatty acids (FFA) and triglycerides (TG) which become non-alcoholic steatohepatitis (NASH). NOTCH-1 receptors act as novel targets for the development of NAFLD/NASH, where overexpression of NOTCH-1 receptor alters the lipid metabolism in hepatocytes leading to NAFLD. SIRT-1 deacetylates the NOTCH-1 receptor and inhibits NAFLD. Hence, computer-aided drug design (CADD) was used to check the SIRT-1 activation ability of cinnamic sulfonyl hydroxamate derivatives (NMJ 1–8), resveratrol, and vorinostat. SIRT-1 (PDB ID: 5BTR) was docked with eight hydroxamate derivatives and vorinostat using Schrödinger software. Based on binding energy obtained (– 26.31 to – 47.34 kcal/mol), vorinostat, NMJ-2, NMJ-3, NMJ-5 were selected for induced-fit docking (IFD) and results were within – 750.70 to – 753.22 kcal/mol. Qikprop tool was used to analyse the pre pharmacokinetic parameters (ADME analysis) of all hydroxamate compounds. As observed in the molecular dynamic (MD) study, NMJ-2, NMJ-3 were showing acceptable results for activation of SIRT-1. Based on these predictions, in-vivo studies were conducted in CF1 mice, where NMJ-3 showed significant (p < 0.05) changes in lipid profile and anti-oxidant parameters (Catalase, SOD, GSH, nitrite, and LPO) and plasma insulin levels. NMJ-3 treatment also reduced inflammation, fibrosis, and necrosis in liver samples.

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Dehydrozingerone protects temozolomide-induced cognitive impairment in normal and C6 glioma rats besides enhancing its anticancer potential

Cited by 19 publications

References 32 publications

Effect of l-Dopa in acute temozolomide-induced cognitive impairment in male mice: a possible antineuroinflammatory role

Effect of l-Dopa in acute temozolomide-induced cognitive impairment in male mice: a possible antineuroinflammatory role

Animal models of chemotherapy-induced cognitive decline in preclinical drug development

Amelioration of high-fat diet (HFD) + CCl4 induced NASH/NAFLD in CF-1 mice by activation of SIRT-1 using cinnamoyl sulfonamide hydroxamate derivatives: in-silico molecular modelling and in-vivo prediction

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